The two objectives of this project will be: 1) to demonstrate that hypothalamic dysfunction is present in both patients with Cushing's disease and in patients with depression associated with dexamethasone nonsuppression though to a differing degree and 2) to show that the affective symptoms associated with corticosteroid abnormalities are more closely related to an increase in by-products of corticosteroid synthesis or an alteration in the ratio of steroids produced than to cortisol itself. These aims will be accomplished by performing a series of endocrine tests on 30 patients with depression associated with dexamethasone nonsuppression, 20 patients with depression and normal suppression, 12 patients with Cushing's disease and 12 normal controls during a 3 1/2 day stay in the Clinical Research Center. The tests which will assess hypothalamic function will include a 24 hour evaluation of the circadian rhythm of ACTH and cortisol and an insulin tolerance test. A vasopressin stimulation test will establish intact function of the pituitary gland and an ACTH stimulation test will determine adrenal reserve. The combination of these tests will also make it possible to establish adrenal responsiveness to endogenous and exogenous ACTH in the different subgroups. Corticosteroid by-products will be measured before and after the administration of ACTH, vasopressin, and insulin to establish whether differences exist between groups. Performing this separation before and after stimulation will also help to determine the extent to which endogenous ACTH is involved in the changes. The results derived from this research project will assist in understanding the pathogenesis of hormone changes in depression and how steroids might be related to the onset of symptoms. On a more practical note, however, this project will help the clinician differentiate the difficult patient who presents as either depressed with associated cortisol abnormalities or a Cushing's disease patient with depression.